1. —K + is high inside cells, Na + is high outside because of the Na+/K+ ATPase (the sodium pump). —Energy is stored in the electrochemical gradient: the chemical and electrical forces across the membrane that arise from the asymmetric distribution of charges and ion concentrations —The intracellular pH is slightly lower than outside. —Cells take great pains to keep cytoplasmic [Ca ++ ] very low. 12-1

2. membrane potential Changes in membrane potential are used by neurons for electrical signalling The actual number of ions that move is small: 1/100,000 th of the concentration can change the membrane potential, V m by 100mV in a typical cell, so ion concentrations are not measurably affected during electrical signalling in neurons.

4. For ions moving down concentration gradient, ∆G<0 Chemical forces: The free energy change for one mole of ions moving across a membrane: ∆G conc = –RT ln C o /C i Electrical forces: The free energy change for charged ion movement: ∆G volt = zFV At equilibrium, the chemical and electrical forces balance: ∆G volt + ∆G conc = 0 (z=1) substituting:

5. 10mM K + Cl – 100mM K + Cl – V eqK+ = 58 mV Log 10 C o /C i = –58 mV by convention V m = V in – V out ion-selective K + channel K+K+ K+K+ + + + + – – – – chemical force electrical force Cl – V eqK+ = 58 mV Log 10 C o /C i

6. Cl – 10mM K + Cl – Cl – 100mM K + Cl – Cl – 100mM Na + Cl – Cl – 10mM Na + Cl – ion-selective K + channel ion-selective Na + channel V eqK+ = 58 mV Log 10 C o /C i = –58 mV by itself V eqNa+ = 58 mV Log 10 C o /C i = 58 mV Both channels together: Na +  in, K +  out; at steady state inward and outward currents match. What will the resting membrane potential (V m ) be? V eq = 58 mV Log 10 C o /C i

7. by opening and closing channels Since the concentration gradients do not change, the membrane potential can be set anywhere between –58 and +58mV simply by changing the ratio between sodium and potassium conductances, i.e., by opening and closing channels. conformation may change to open and close gated channel + Cl – 10mM K + Cl – Cl – 100mM K + Cl – + Cl – 100mM Na + Cl – Cl – 10mM Na + Cl – The resting potential depends on how fast ions flow through each channel, the relative conductance.

8. Chemiosmotic coupling electrochemical gradient Energy is stored in the electrochemical gradient: the chemical and electrical forces across the membrane that arise from the asymmetric distribution of charges and ion concentrations Mitochondria use energy from electrons (e – ) to pump protons (H + ) across a membrane and then use the electrochemical gradient to make ATP.

9. The resting potential for most cells is negative (–20 to –200mV) because real cells are permeable to both K + and Cl –, but have low Na+ permeability. K + would flow out (conc. gradient) and Cl – in (due to V m and intracellular anions), and H 2 O would flow in. However, the driving force for Na +  in is high, driving V m  0. Counteracting this is the electrogenic Na + / K + ATPase.

10. Proton-motive force Electrical forces Electrical forces: The free energy change for charged ion movement: ∆G volt = zFV m are large compared to Chemical forces Chemical forces: The free energy change for one mole of ions moving across a membrane: ∆G conc = RT ln C matrix /C cytosol The Nernst Equation Electrical forces Chemical forces ∆pH = pH matrix – pH cytosol pmf = V m + 2.3RT ∆pH/F

11. Proton-motive force is used to drive ATP synthesis ATP synthase can go backwards and hydrolyze ATP inner membrane

12. Oxidative phosphorylation ATP synthase - an amazing machine! 100 ATPs per second 1 ATP for 3 H +

13. ATP synthase